红白血病

摘要： 目的 探讨异藤黄酚对小鼠红白血病CB3细胞增殖以及凋亡的影响.方法 用噻唑蓝(MTT)法检测细胞增殖情况.根据MTT结果,将给药后细胞分为低、中、高3个浓度实验组(2.5,5.0,和10.0μmol·L-1异藤黄酚,处理48 h);未给药细胞作为空白组.用流式细胞术检测CB3细胞凋亡的情况,蛋白质印迹法检测异藤黄酚作用于细胞后聚腺苷二磷酸核糖聚合酶(PARP)和胞活化的磷酸化胞外信号调节激酶(p-ERK)蛋白表达水平.结果 异藤黄酚可显著抑制小鼠红白血病CB3细胞的增殖,半数抑制浓度(IC50)为(8.19±0.63)μmol·L-1.空白组和低、中、高3个浓度实验组的细胞凋亡率分别为(1.30±0.22)％,(1.80±0.23)％,(2.50±0.52)％和(64.50±3.35)％.给药12 h后,这4组的PARP蛋白相对表达量分别为1.00±0.08,0.86±0.02,0.68±0.12和0.57±0.11;这4组的p-ERK蛋白相对表达量分别为1.00±0.02,0.57±0.13,0.54±0.02和0.05±0.01.上述指标:高浓度实验组与空白组比较,差异均有统计学意义(均P<0.05).结论 异藤黄酚可通过诱导CB3细胞发生凋亡,从而抑制细胞的增殖.其诱导CB3细胞凋亡可能与其调控PARP和p-ERK的表达有关.

摘要： 目的 探讨氢醌(HQ)对红白血病细胞株K562细胞周期的影响及其作用机制.方法 取生长至对数期时K562细胞,设空白对照组及HQ染毒低剂量组、中剂量组、高剂量组,分别以HQ终浓度为0、15、30、60μmol/L处理,各实验组间隔处理72 h后,流式细胞术检测细胞周期分布,免疫印迹法检测CDC25A、CDK2、Cyclin E、Cycli-n A、p53、p21、PCNA等细胞周期相关蛋白表达.结果 空白对照组及HQ染毒低剂量组、中剂量组、高剂量组G0/G1期细胞所占比例分别为55.90％±2.71％、40.16％±3.34％、29.97％±1.23％、32.84％±0.93％,S期细胞比例分别为43.42％±2.61％、57.01％±3.50％、66.87％±1.77％、66.66％±0.31％,G2/M期细胞比例分别为0.73％±0.78％、3.27％±2.05％、4.40％±5.07％、0.18％±1.54％,与空白对照组比较,各染毒剂量组G0/G1细胞比例下降,S期细胞比例增加(P ＜0.05),G2/M期细胞差异无统计学意义(P＞ 0.05).与空白对照组比较,CDC25A蛋白表达在HQ染毒各剂量组降低(P ＜0.05),HQ染毒各剂量组间高剂量组＜中剂量组＜低剂量组(P ＜0.05).与空白对照组比较,Cyclin E、PCNA蛋白表达在HQ染毒低剂量组差异无统计学意义,在中、高剂量组表达量降低(P ＜0.05),HQ染毒各剂量组间高剂量组＜中剂量组＜低剂量组(P ＜0.05).与空白对照组比较,p53蛋白在HQ染毒低、中剂量组表达量增高(P ＜0.05),在高剂量组表达差异无统计学意义,HQ染毒各剂量组间高剂量组＜中剂量组＜低剂量组(P ＜0.05).CDK2、Cyclin A和p21蛋白在空白对照组与HQ染毒各剂量组间的表达差异无统计学意义(P＞ 0.05).结论 HQ致K562细胞周期发生S期阻滞,可能与其下调CDC25A、Cyclin E、PCNA蛋白表达有关.%Objective To investigate the effect of hydroquinone (HQ) on the cell cycle of erythroleukemia cell line K562 and its mechanism. Methods K562 cells in the logarithmic phase were selected and then divided into the blank control group and HQ-treated low-dose group, medium-dose group and high-dose group which were treated with 0, 15, 30, and 60 μmol/L HQ for 72 h at intervals and repeatedly. After 72 h, the cell cycle distribution was detected by flow cytometry, and cell cycle-related protein expression such as CDC25 A, CDK2, CyclinE, CyclinA, p53, p21 and PCNA was detected Western blotting. Results The results of flow cytometry showed that the ratio of cells in the G0/G1 phase of the blank control group and low-dose, medium-dose and high-dose HQ groups was 55. 90％ ± 2. 71％, 40. 16％ ± 3. 34％, 29. 97％± 1. 23％, and 32. 84％ ± 0. 93 ％, and the ratio of cells in the S phase was 43. 42％ ± 2. 61％, 57. 01％ ± 3. 50％, 66. 87％ ± 1. 77％, and 66. 66％ ± 0. 31％, and the ratio of cells in the G2/M phase was 0. 73％ ± 0. 78％, 3. 27％ ±2. 05％, 4. 40％ ± 5. 07％, and 0. 18％ ± 1. 54％, respectively. Therefore, HQ could decrease the proportion of cells in the G0/G1 phase in the K562 cell cycle (P ＜ 0. 05), increase the proportion of cells of the S phase (P ＜ 0. 05), and induce S phase arrest. Western blotting showed that compared with the blank control group, the expression of CDC25 A protein decreased in each HQ dose group (P ＜ 0. 05), and the expression of the high-dose to medium-dose and low-dose HQgroups decreased (P ＜ 0. 05). Compared with the blank control group, the expression of CyclinE and PCNA protein in the low-dose group was not statistically different, but the expression in the medium-dose and high-dose HQ groups decreased (P ＜ 0. 05). The expression of CyclinE and PCNA protein from the high-dose group to medium-does group and low-dose groups decreased in turn after exposure of HQ (P ＜ 0. 05). Compared with the blank control group, the expression of p53 protein in the low-does and medium-dose groups increased (P ＜ 0. 05), and the difference in the high-dose group was not statistically significant. There was no significant difference in the expression of CDK2, CyclinA or P21 protein between the blank control group and HQ dose groups (all P＞ 0. 05). Conclusion HQ can induce S phase arrest in K562 cells which might be related to the down-regulated expression of CDC25 A, CyclinE, and PCNA.

摘要： ①目的 采用尾静脉注射制备小鼠红白血病模型,探讨α-半乳糖苷神经酰胺(α-Galcer)对红白血病发生和发展的影响.②方法 体外培养小鼠红白血病细胞系FBL-3,经尾静脉注射接种C57BL/6小鼠.将FBL-3接种小鼠进一步分为α-Galcer处理组和溶剂对照处理组,于FBL-3接种当天分别注射α-Galcer和溶剂DMSO.观察不同处理组FBL-3细胞接种小鼠总体变化,并于FBL-3接种后第8周处死小鼠,观察外周血血象变化和肿瘤结节形成情况.③结果 与正常小鼠相比,FBL-3细胞接种小鼠实验期间皮肤感染增加.外周血有核红细胞增加,并且出现明显的实体器官肿瘤结节,而α-Galcer处理显著抑制实体器官肿瘤结节的形成.④结论 通过FBL-3细胞尾静脉注射初步建立红白血病肿瘤小鼠模型,α-Galcer处理对小鼠白血病的发展发挥抑制作用.%Objective To prepare erythroleukemia mouse model through tail vein injection of FBL-3 cell and investigate the effect of α-Galcer on the occurrence and development of erythroleukemia.Methods FBL-3 erythroleukemia cells were cultured in vitro and C57BL/6 erythroleukemia mouse models were prepared by tail vein injection of FBL-3 cells.The FBL-3 injected mice were further divided into two groups by injecting α-Galcerand solvent DMSO respectively on the date of FBL-3 injection.The overall changes of FBL-3 injected mice in each group were observed during this experiment.8 weeks after FBL-3 injection, the FBL-3 injected mice were killed and peripheral blood and tumor nodules formation were detected.Results Compared with normal C57BL/6 mice, the FBL-3 injected mice demonstrated obvious skin infection, increased nucleated red blood cells and apparent tumor nodules formation, whileα-Galcer treatment significantly inhibited the formation of tumor nodules on solid organs.Conclusion Erythroleukemia mouse models were prepared preliminarily by tail intravenous injection of FBL-3 cells, and α-Galcer treatment exhibited an inhibitory effect on the development of leukemia in mice.

摘要： （1）目的 采用尾静脉注射制备小鼠红白血病模型,探讨α-半乳糖苷神经酰胺（α-Galcer）对红白血病发生和发展的影响。（2）方法 体外培养小鼠红白血病细胞系FBL-3,经尾静脉注射接种C57BL/6小鼠。将FBL-3接种小鼠进一步分为α-Galcer处理组和溶剂对照处理组,于FBL-3接种当天分别注射α-Galcer和溶剂DMSO.观察不同处理组FBL-3细胞接种小鼠总体变化,并于FBL-3接种后第8周处死小鼠,观察外周血血象变化和肿瘤结节形成情况。（3）结果 与正常小鼠相比,FBL-3细胞接种小鼠实验期间皮肤感染增加。外周血有核红细胞增加,并且出现明显的实体器官肿瘤结节,而α-Galcer处理显著抑制实体器官肿瘤结节的形成。（4）结论 通过FBL-3细胞尾静脉注射初步建立红白血病肿瘤小鼠模型,α-Galcer处理对小鼠白血病的发展发挥抑制作用。

摘要： 目的：探讨利用阿霉素诱导小鼠红白血病MEL细胞免疫原性死亡的实验进行研究.方法：采用小鼠随机实验对比方法,共选择60只成年雄性小白鼠,将其随机分为三个小组,分别是红白血病对比组;空白对比组和阿霉素诱导组,每小组共20只小白鼠.其中红白血病对比组采用尾部静脉注射无菌磷酸盐缓冲剂200,然后在8天后为小鼠注射MEL细胞200（细胞密度为）.阿霉素诱导组小鼠注射的MEL细胞需要和阿霉素进行诱导培养超过24小时,共注射200（细胞密度为）.空白对比组不注射任何药物,分别记录三组小白鼠的患病情况、生存时间和外周血白细胞含量.结果：根据研究结果可以看出,阿霉素浓度越大就会导致MEL细胞凋亡率越大.红白血病对比组当中首只死亡小鼠出现在注射后第13天,而阿霉素诱导组则发生于注射后第35天.同时红白血病对比组小鼠血液当中外周血白细胞含量为10.29,而阿霉素诱导组则仅为8.57.两组数据存在较大差异,具有统计学意义（P 〈0.05）.结论：阿霉素具有促进MEL细胞凋亡的作用,对小鼠红白血病有着极好的治疗和预防效果.

摘要： This study was purposed to investigate the therapeutic effects of early transfusion of immunized donor lymphocytes after haploidentical transplantation by means of mouse model of nonmyeloablative haploidentical bone marrow transplantation.CB6F1 female mouse was served as recipient and C57BL/6 male mouse was served as donor.Each CB6F1 female mouse was subjected to intravenous transfusion with 1 × 106 erythroleukemia (EL9611) cells at day 4 before transplantation,followed with intraperitoneal injection of Ara-C (0.015 g) respectively at day 2 and day 1,then conditioned for BMT with TBI (450 cGy) at day 1 before transplantation.After conditioning (day 0),each of recipients was transplanted with 6 × 107 mixture of bone marrow and spleen cells from the C57BL/6 mice,and was infused with 6 × 107 immunized donor lymphocytes at day 15 after transplantation.All treated animals were evaluated for survival,development of leukemia and aGVHD.The donor CD3 + cell chimerism and sex determining region Y gene (SRY) in recipients were monitored periodically after transplantation.The results showed tht all mice with only inoculation of 106 EL9611 cells survived for 15 ± 1 days (n =4) ; all mice of other groups obtained the varying degrees of implantation.SRY could be detected at day 30 and 60 after transplantation.The chimerism of donor CD3 + cells in mixed bone marrow transplantation (MT) group at day 14,30 and 60 respectively reached 17.95％ ± 12.03％,37.34％ ±2.78％ and 47.06％ ±6.1％.In donor lymphocyte infusion (DLI) group it reached 69.78％ ± 12.62％,75％ ± 15.97％,83.41％ ± 16.07％ at day 30,45 and 60 after transplantation.The mice of MT and DLI group survived for 66.66 ± 1.47 days and 78.2 ± 7.82 days.It is concluded that the high tumor burden before transplantation can affect donor cell engraftment and prognosis.Early post-translanted infusion of immunized lymphocytes from donor can help to improve the therapeutic efficacy and survival.%本研究在小鼠非清髓性单倍体骨髓移植模型上,观察移植后早期输注供体免疫细胞对促进植入及改善疗效的作用.以CB6F1雌性小鼠为受鼠,C57 BL/6雄性小鼠为供鼠,移植前4d经尾静脉注射小鼠红白血病细胞1×106个/只,移植前2d和1d分别通过腹腔注射阿糖胞苷0.015g/只,移植前1d予450 cGy全身照射(TBI),移植当天给予供鼠骨髓及脾细胞混合物6 ×10 7个/只,移植后15 d输注供体免疫淋巴细胞6×10 7个/只,移植后定期监测受鼠外周血供鼠CD3+细胞嵌合状态和供鼠性别决定基因(SRY),观察小鼠急性移植物抗宿主病(aGVHD)、疾病复发及生存情况.结果表明:经尾静脉注射小鼠红白血病细胞1×106个/只,不予治疗,小鼠平均生存期为15±1d;混合骨髓移植组移植后供者细胞获得植入,SRY基因在移植后30和60 d时检测PCR结果均阳性,移植后14、30、60d外周血供鼠CD3+细胞嵌合率分别为(17.95±12.03)％、(37.34±2.78)％,(47.06±6.1)％；DLI组移植后30、45、60 d嵌合率为(69.78±12.62)％、(75±15.97)％、(83.41±16.07)％；小鼠移植后平均生存期分别为66.66±1.47 d、78.2±7.82 d.结论:移植前高肿瘤负荷影响供体细胞植入及预后,移植后早期行供体免疫淋巴细胞输注可以进一步改善治疗效果,延长生存期.

摘要： 目的 探讨毛冬青甲素对红白血病K562细胞凋亡的表达机制.方法 MTT比色法测定细胞增殖的抑制率;电镜下观察细胞凋亡形态变化;RT-PCR法和流式细胞术(FCM)检测毛冬青甲素对K562细胞survivin和bax表达影响.结果 毛冬青甲素对K562细胞生长有抑制作用,并呈剂量一时间效应关系.毛冬青甲素处理细胞后可见凋亡形态学变化,细胞核染色质浓缩,电子密度增加,细胞质内出现空泡化.RT-PCR法和FCM检测结果显示毛冬青甲素可抑制survivin上调,促进bax的表达.结论 毛冬青甲素能诱导K562细胞凋亡,其机制可能与调节survivin和bax的表达有关.

摘要： Objective: Acute erythroid leukemia is rare.Clone switch in acute leukemia at relapse is an uncommom event, and therefore rarely reported in the literature. To improve the recognition of acute erythroid leukemia and mechanism of clone switch, here we report a case of acute monocytic leukemia switching to acute erythroid leukemia at relapse. Methods: To analyse a case of clone switch from acute monocytic leukemia to acute erythroid leukemia and get information at morphologic, cytogenetic and molecular levels during the treatment by some tests. Results: At initial diagnosis, the patient was acute monocytic leukemia. And switched to acute erythroid leukemia by analysis of results at morphologic, cytogenetic and molecular level after a cycle of chemotherapy. After another cycle of chemotherapy, the patient got a remission at morphologic level, and discharged. Afterwards.the patient gave up the treatment and died after 2 months. Conclusions: There would be two reasons to explain the clone switch: Firstly, the disorders come from the progenitor of red cells and monocytes, then cause the disease. As well, the disorders may come from impaired early hemapoietic stem cell(hsc), leading to the monocytic and erythropoietic abnormalities. Secondly, the changes of bone marrow microenvironment induced erythroid abnormalities which lead to acute erythroid leukemia. In this case, the disease may have abnormalities in early hematopoietic stem cells, and the bone marrow microenvironment played an important role in the process of the disease. The results need to affirmed by further clinical observation and further researches. It remind us that dynamic diagnosis and consciousness of treatment need to improved, Which will contribute to the prevention, diagnosis and treatment of acute leukemia.%目的:红白血病为临床少见的急性髓系白血病亚型,白血病克隆转换不常见,在国内外文献中有关报道少见.通过对一例由急性单核细胞白血病转化的急性红白血病(acute erythroid leukemias,AEL)的病例分析,学习并探讨急性红白血病的临床特点及实验室检查特征,提高对急性红白血病疾病特点及白血病克隆转化的认识.方法:报道一例初诊为急性单核细胞白血病,后转为急性红白血病的患者.期间对其进行持续的细胞形态学,遗传学及分子生物学监测.结果:患者首次入院诊断为急性单核细胞白血病,经过一个疗程化疗后,骨穿显示从急性单核细胞白血病转为急性红白血病.随后再进行了一个疗程化疗,化疗结束后患者好转出院.后因经济原因,患者未继续治疗,2月后随访,患者死亡.结论:本例急性单核细胞性白血病化疗后转为红白血病.究其机制,可能有:一.发病是粒-单定向祖细胞和红系定向祖细胞同时受损,只是早期单核细胞系异常表现明显,红系异常早期表现不明显.或疾病起源于更早期造血干细胞,导致单核系和红系均有异常.二.在疾病过程中,骨髓微环境的变化,诱导红系异常而导致红白血病的发生.经过分析,本病例中,疾病可能起源于更早期造血干细胞的可能性较大,而骨髓微环境在疾病变化过程中则起到了重要的作用.这一结果有待进一步临床观察研究和肯定.提醒临床医生,提高动态的诊断和治疗意识,将有助于该疾病的预防、诊断和治疗.

摘要： AIM: To establish an acute graft - versus - host disease ( GVHD ) model in EL9611 erythroleukemia mice.METHODS: Using C57BL/6 ( H - 2b ) mice as the donor and BALB/c ( H - 2d ) mice as the recipient in allogeneic bone marrow transplantation ( allo - BMT ), the acute GVHD model was established.The mice were divided into leukemia group ( n = 10 ), radiation control group ( leukemic mice given radiation without allo - BMT, n = 4 ), GVHD group ( leukemic mice given radiation + allo - BMT, n = 10 ) and normal control group ( n = 4 ).In leukemia group, 2 × 106/mouse EL9611 erythroleukemic cells were transfused via tail vein into BALB/c mice to build the erythroleukemia model.In GVHD group, 7 days after leukemic cell transfusion, the mice received total dose of 8.0 Gy [60Co]γ of total body irradiation( TBI ), and within 5 h, 2 × 10 C57BL/6 bone marrow cells and 1 × 10 C57BL/6 spleen cells per mouse were transfused via tail vein to build the acute GVHD model in EL9611 erythroleukemia mice.The clinical manifestations of posture , fur, stool and so on were observed.Pathological examination was conducted to examine the changes of liver, spleen, skin, small intestine and peripheral blood.The survival rate was also calculated.RESULTS: ( 1 ) In leukemia group, the mean survival time ( MST ) was ( 14.5 ± 2.1 ) days, or ( 7.5 ± 0.7 ) days when irradiation day was as day 0( P ＜ 0.01 compared with GVHD group ).The death rate was 100％ with no spontaneous remission.The dead mice showed splenohepatomegalia [liver weight ( 2.40 ±0.48 ) g, spleen weight ( 0.84 ±0.20 ) g, P ＜0.01 compared with normal group]and high WBC count [( 3.33 ±0.27 ) × 1010/L prior to death, P ＜0.05, compared with normal group].Pathological examination showed disorganization of normal tissues and leukemic cell infiltration.( 2 ) In radiation control group, MST was ( 9.0 ± 0.7 ) d, with significant difference as compared with GVHD group and normal group ( P ＜ 0.01 ).The death rate was 100％.Pathological examination showed hematopoiesis exhaustion.( 3 ) In GVHD group, MST was ( 32.0±3.2)d(P＜ 0.01 compared with other groups ).The death rate was 100％ , the symptoms were observed on day 10 - 13 after allo-BMT.Clinical manifestations and pathological examination corresponded to those of Ⅰ degree to Ⅱ degree of GVHD.CONCLUSION: Intravenous infusion of 2 × 106/mouse EL9611 leukemic cell successfully establishes the EL9611 erythroleukemia animal model.Seven days after EL9611 leukemic cell transfusion, lethal dose of TBI and allo - BMT can successfully build the acute GVHD model of EL9611 leukemic mice.%目的:建立EL9611红白血病小鼠急性移植物抗宿主病(GVHD)的动物模型.方法:同种异基因骨髓移植(allo-BMT)以C57BL/6(H-2b)鼠为供鼠,BALB/c(H-2d)为受鼠.设白血病组(n=10)、照射对照组(白血病鼠照射后不进行allo-BMT,n=4)、GVHD组(白血病鼠照射+allo-BMT,n=10)及正常对照组(n=4).白血病组采用每只BALB/c鼠尾静脉输注2×106个EL9611红白血病细胞建立红白血病动物模型;GVHD组于接种白血病细胞7 d后行总剂量为8.0 Gy的1次性[60Co]γ射线全身照射(TBI),照射后5 h内每只小鼠尾静脉输注C57BL/6鼠骨髓细胞2×106个+脾细胞1×107个,建立EL9611红白血病小鼠的急性GVHD动物模型.观察小鼠体位、皮毛、大便等临床表现,病理检查肝脾、皮肤、小肠、外周血和骨髓,计算生存率.结果:白血病组生存时间(14.5±2.1) d[从照射当天(第0 d)算起为(7.5±0.7) d],生存时间与GVHD组相比P<0.01,死亡率100%,无自发缓解,死亡时肝脾肿大(肝重2.40 g±0.48 g,脾重0.84 g±0.20 g,与正常对照组比P<0.01),外周血WBC升高[死亡前(3.33±0.27)×1010/L,与正常对照组比P<0.05],病理检查示组织正常结构破坏,白血病细胞浸润.照射对照组生存时间为(9.0±0.7) d,生存时间与GVHD组和正常对照组相比差异显著(P<0.01),死亡率100%,病理检查显示造血衰竭.GVHD组生存时间为(32.0±3.2)d,生存时间与其它各组相比P<0.01,死亡率100%,allo-BMT后第10-13 d出现症状,临床表现和病理检查符合Ⅰ到Ⅱ度GVHD的改变.结论:采用EL9611红白血病细胞(2×106/鼠)静脉输注的方式可成功建立EL9611红白血病动物模型;接种EL9611红白血病细胞第7 d行TBI +allo-BMT可成功建立EL9611红白血病小鼠的急性GVHD动物模型.

摘要： 目的:白血病化疗药物的毒副反应极其耐药性仍是尚未解决的难题,本项目受科技部"十一五"重大新药创制专项资助,自行提取分离出多个中药有效部位或成分,采用抗白血病的生物学活性试验,筛选并确定了作用最佳的低极性人参皂苷ALK,成分含量明确.前期实验证明ALK通过抑制白血病细胞增殖、促进凋亡、增强化疗药敏,并阻滞异常增殖的恶性信号传导而抗白血病.本文在此基础上，采用细胞学和动物模型实验，研究ALK体内外对红白血病K562细胞的抑制增殖、阻滞细胞增殖周期及诱导分化的作用，并通过对特异性BCR/ABL融合蛋白，信号传递途径和分化相关蛋白等方面的研究，探索ALK抗白血病的作用机制。rn 方法:① MTT法和半固体集落培养检测不同浓度的ALK抑制K562细胞增殖的作用。②流式细胞术分析ALK处理对白血病细胞增殖周期的影响。③Western blot分析增殖相关信号传递途径蛋白激酶的表达。④采用皮下接种高增殖潜能K562细胞，建立荷白血病瘤裸鼠模型，ALK低、中和高剂量灌胃治疗4周，阳性对照药高三尖杉醋碱。⑤免疫细胞化学、激光共聚焦显微术和Western Blot检测体外白血病细胞和体内皮下瘤组织BCR/ABL融合蛋白，及分化相关GATA-1转录因子和γ-珠蛋白的表达。rn 结果:①体外培养体系中ALK20-100mg/L有效地抑制白血病细胞增殖，呈时间和剂量依赖性，液体培养的抑制率25.5±17.7%-66.1±13.3%半固体培养集落生成的抑制率37.7±16.8%-83.8±5.8%.②中剂量ALK 60mg/L阻滞细胞进入增殖周期，S期细胞率下降为37.8±3.2%，明显低于对照组的54.7±0.3%。增殖指数从52.8±0.8%下降为30.3±0.5%.③免疫细胞化学、激光共聚焦显微术和Western Blot显示ALK处理后，K562细胞内BCR/ABL融合蛋白的表达水平明显降低。④Western Blot显示ALK能够不同程度地抑制K562细胞内AKT-1、AKT-2、ERK-2、MEK-1和MEK-2等增殖相关蛋白激酶的表达水平。⑤小剂量ALK孵育细胞14d，免疫细胞化学显示分化相关GATA-1转录因子和γ-珠蛋白表达强阳性细胞率分别为40.8±10.5%和62.0±5.6%，明显高于对照组的23.6±3.2%和21.3±7.3%，激光共聚焦显微术和Western Blot也证实了同样结果。)ALK有效地抑制荷瘤裸鼠体内瘤体的生长，ALK低、中、高剂量治疗组的抑瘤率分别为35.1%, 61.6%和72.9%。病理检查显示ALK中、高剂量治疗组的瘤组织有不同程度的坏死现象，白血病瘤细胞出现肿胀、破裂，胞核溶解等，并有不同程度的分化趋向。⑦免疫组化染色显示ALK中、高剂量组的瘤组织分化相关GATA-1转录因子和γ-珠蛋白表达的水平明显增高。rn 结论:ALK在体内外有效地抑制K562白血病细胞的增殖，阻滞细胞进入增殖周期，治疗白血病荷瘤裸鼠的体内疗效显著，其作用机制通过抑制特异性BCR/ABL融合蛋白的表达，并阻滞异常增殖恶性信号的传导。鉴于白血病细胞是难以分化的，ALK体内外诱导白血病细胞分化的作用显著，是药效学研究的突破点，具有重要的应用价值，其作用机制不同于传统化疗药物，可通过上调分化相关转录因子和蛋白的表达而抗白血病。上述结果提示ALK是抗白血病的有效成分，为中药5类新药的开发奠定基础，可望成为安全有效抗白血病的中药新药。

摘要： 探讨三氧化二砷(AS2O3)在体外对人红白血病多药耐药细胞株(K562／ADM，以下简称为K562／A)的影响，并观察其与化疗药物联合治疗难治性白血病的临床疗效。

摘要： 本发明涉及以对造血干细胞生长因子(SCGF)进行定量为特征的对白血病、前白血病或非白血病性恶性血液疾病进行判定的方法、对白血病与前白血病或非白血病性恶性血液疾病进行区别的方法、对再生障碍性贫血和骨髓发育异常综合征进行区别的方法、对造血干细胞移植后的造血干细胞的存活的状态进行判定的方法、或对移植物抗宿主病进行判定的方法。还涉及作为有效成分含有与造血干细胞生长因子(SCGF)反应的抗体的白血病、前白血病或非白血病性恶性血液疾病的诊断药、造血干细胞移植后的造血干细胞的存活延迟或移植物抗宿主病(GVHD)的诊断药。

摘要： 本文提供了使用某些生物标志物诸如基因集(例如，白血病干细胞(LSC)特征)预测和监测患有各种疾病和障碍诸如癌症(例如，淋巴瘤、多发性骨髓瘤(MM)、和白血病诸如急性髓系白血病(AML))的患者对某些化合物的临床敏感性和治疗反应的方法。本文还提供了使用所述治疗化合物治疗疾病的方法。

摘要： 本发明公开了一种用于白血病干细胞抑制增殖及诱导分化的小分子，所述小分子为甲基牛扁亭；本发明的优点在于：能够作为治疗初诊以及复发难治性AML的有效药物。

摘要： 本发明公开了一种白血病标志物，所述白血病标志物为SEQ ID No.1所示的基因或与其具有85％‑99％同源性的基因，该标志物用于制备预测、诊断患者是否为难治髓系白血病患者，或分选难治髓系白血病患者，以及预测、诊断患者是否为经治疗达到骨髓完全缓解后出现复发风险的髓系白血病患者，或分选经治疗达到骨髓完全缓解后出现复发风险的髓系白血病患者，以及预测或评估髓系白血病患者总生存期的产品。在化疗前检测该标志物可判断患者对化疗的反应性和复发情况以及预后生存情况，能够将化疗敏感和难治、复发的患者很好地区分，拟补了现有危险度分层的不足，达到对患者进一步精细分层的目的，有效指导后续化疗和移植等治疗方案。

摘要： 本发明公开了一种双裂孕烷型甾体化合物在制备抗红白血病药物中的应用，属于生物学和医药学技术领域。本发明所述双裂孕烷型甾体化合物为C21甾体皂苷BW18。通过MTT检测发现，不同浓度的BW18均能抑制HEL的细胞活力，具有浓度依赖性。经过流式细胞仪和Western blot检测表明，BW18主要通过上调P27，下调c‑Myc、cyclin E1、CDK1和CDK2周期相关蛋白的表达而诱导HEL细胞发生G2期周期阻滞，同时调控红系和巨核系分化相关基因的表达，促进细胞向红系和巨核系分化，从而抑制红白血病的发生。BW18可作为治疗红白血病的潜在小分子，为红白血病的治疗药物开发提供研究基础。

摘要： 本发明公开了一种急性红白血病KEL基因及其转录出的环状RNA(circ‑KEL)分子标记物以及相关的检测试剂。与现有技术相比，本发明的检测试剂具有检测灵敏度高、特异性强、快速且检测方法简单。

摘要： 本发明提供一种红白血病小鼠动物模型的构建方法，属于动物模型构建技术领域。本发明所述构建方法包括以下步骤：收集F‑MuLV病毒上清液，将F‑MuLV病毒上清液注射到出生48h内的乳鼠中，即得红白血病小鼠动物模型。本发明所述构建方法操作简单、成功率高，构建的红白血病小鼠动物模型存活时间长。

摘要： 本发明公开了一种双裂孕烷型甾体化合物在制备抗红白血病药物中的应用，属于生物学和医药学技术领域。本发明所述双裂孕烷型甾体化合物为C21甾体皂苷BW18。通过MTT检测发现，不同浓度的BW18均能抑制HEL的细胞活力，具有浓度依赖性。经过流式细胞仪和Western blot检测表明，BW18主要通过上调P27，下调c‑Myc、cyclin E1、CDK1和CDK2周期相关蛋白的表达而诱导HEL细胞发生G2期周期阻滞，同时调控红系和巨核系分化相关基因的表达，促进细胞向红系和巨核系分化，从而抑制红白血病的发生。BW18可作为治疗红白血病的潜在小分子，为红白血病的治疗药物开发提供研究基础。

摘要： 本发明公开了一种延缓和治疗红白血病的组合物，该组合物中含有石蒜碱。所述石蒜碱可以通过抑制JAK/STAT3信号通路从而阻滞人红白血病细胞(HEL，Human Erythroleukemia cell line)的细胞周期，诱导其向红系分化成熟，发挥抗红系白血病作用，所述石蒜碱的作用靶点为XPO7，其促红系分化作用与其下游XPO7有关，是一种潜在的高效、低毒临床药物或先导化合物。

摘要： 本发明公开了一种急性红白血病KEL基因及其转录出的环状RNA(circ‑KEL)分子标记物以及相关的检测试剂。与现有技术相比，本发明的检测试剂具有检测灵敏度高、特异性强、快速且检测方法简单。